Innate Immune Defences & Inflammation 1 Flashcards

1
Q

What is Innate Immunity?

  • … line of defence against infection
  • Present at … and passed down …
  • Occurs within … of … …
A
  • First line of defence against infection
  • Present at birth and passed down genetically
  • Occurs within minutes of pathogen recognition
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2
Q

… immunity is the first line of defence against infection

A

Innate immunity

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3
Q

Innate Immunity is present at …

A

birth - passed down genetically

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4
Q

How is innate immunity passed down?

A

genetically

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5
Q

Innate immunity occurs within … of pathogen recognition

A

Innate immunity occurs within minutes of pathogen recognition

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6
Q

The Innate Immune System is a … response

A

The Innate Immune System is a rapid response

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7
Q

The Innate Immune System is a … response

A

The Innate Immune System is a rapid response

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8
Q

Innate Immune Response - Immediate vs Induced Response

  • The immediate innate immune response - … to … hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - … hours to … days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
A
  • The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
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9
Q

Innate Immune Response - Immediate vs Induced Response

  • The … innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The … innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
A
  • The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
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10
Q

Innate Immune Response - Immediate vs Induced Response

  • The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed … … molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit … cells to infected tissue - inflammation, fever etc)
A
  • The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
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11
Q

Innate Immune Response - Immediate vs Induced Response

  • The immediate innate immune response - … to … hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - … hours to … … (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
A
  • The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
  • The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
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12
Q

Characteristics of Innate Immunity

  • … encoded - Inherited in …
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers … response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
A
  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
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13
Q

Characteristics of Innate Immunity

  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes … classes of pathogens
  • Interacts with a … of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
A
  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
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14
Q

Characteristics of Innate Immunity

  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene …
  • No … distribution
  • Able to discriminate between even closely related molecular structures
A
  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
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15
Q

Characteristics of Innate Immunity

  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple … …
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
A
  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
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16
Q

Characteristics of Innate Immunity

  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers … response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • … to discriminate between even closely related molecular structures
A
  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
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17
Q

Characteristics of Innate Immunity

  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes … classes of …
  • Interacts with a range of … structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
A
  • Germline encoded - Inherited in genome
  • Expressed by all cells of a particular type - e.g macrophages
  • Triggers immediate response
  • Recognizes broad classes of pathogens
  • Interacts with a range of molecular structures of a given type
  • Does not encode in multiple gene segments
  • Does not require gene rearrangement
  • No Clonal distribution
  • Able to discriminate between even closely related molecular structures
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18
Q

Innate Immune Memory (trained immunity)

  • Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
  • Trained immunity occurs due to … modifications triggered by the initial infection.
A
  • Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
  • Trained immunity occurs due to epigenetic modifications triggered by the initial infection.
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19
Q

Innate Immune Memory (trained immunity)

  • Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
  • Trained immunity occurs due to epigenetic modifications triggered by the … …
A
  • Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
  • Trained immunity occurs due to epigenetic modifications triggered by the initial infection.
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20
Q

Innate Barriers to Infection

  • … barriers - skin, respiratory tract, gastrointestinal tract
  • … barriers - Complement, Defensins, Collectins
  • … barriers - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
A
  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble barriers - Complement, Defensins, Collectins
  • Induced barriers - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
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21
Q

Innate Barriers to Infection

  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - …, Defensins, Collectins
  • Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), I…
A
  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - Complement, Defensins, Collectins
  • Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
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22
Q

Innate Barriers to Infection

  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - Complement, Defensins, Collectins
  • Induced - Innate Immune cells, … … … (PRRs), Interferon
A
  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - Complement, Defensins, Collectins
  • Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
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23
Q

Innate Barriers to Infection

  • Physical barriers - …, respiratory tract, gastrointestinal tract
  • Soluble - Complement, …, Collectins
  • Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
A
  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - Complement, Defensins, Collectins
  • Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
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24
Q

Innate Barriers to Infection

  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - Complement, Defensins, Collectins
  • Induced - … … cells, Pattern Recognition Receptors (PRRs), Interferon
A
  • Physical barriers - skin, respiratory tract, gastrointestinal tract
  • Soluble - Complement, Defensins, Collectins
  • Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
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25
_Innate Barriers to Infection_ * Physical barriers - skin, respiratory tract, gastrointestinal tract * Soluble - Complement, Defensins, ... * Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
* Physical barriers - skin, respiratory tract, gastrointestinal tract * Soluble - Complement, Defensins, **Collectins** * Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
26
These are all examples of ... barriers to infection
**Innate barriers to infection**
27
These are all examples of ... barriers to infection
**Innate barriers to infection**
28
_Anatomical Barriers to Infection_ * Skin has a dense layer of dead ... that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the ... that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
* Skin has a dense layer of dead **keratinocytes** that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the **surfactant** that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
29
_Anatomical Barriers to Infection_ * Skin has a dense layer of dead keratinocytes that act as a ... barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel ..., whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
* Skin has a dense layer of dead keratinocytes that act as a **physical** barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel **mucus**, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
30
_Anatomical Barriers to Infection_ * Skin has a dense layer of dead keratinocytes that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate ... * In the gut, people unable to secrete sufficient gastric acid have a high risk of ... infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
* Skin has a dense layer of dead keratinocytes that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate **complement**. * In the gut, people unable to secrete sufficient gastric acid have a high risk of **salmonella** infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
31
_Anatomical Barriers to Infection_ * Skin has a dense layer of dead keratinocytes that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst ... in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your ...
* Skin has a dense layer of dead keratinocytes that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst **macrophages** in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your **microbiome**.
32
_Anatomical Barriers to Infection_ * Skin has a dense layer of dead keratinocytes that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by ... ...). In the lower airways there are collectins in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is ... with ‘good’ bacteria that form your microbiome.
* Skin has a dense layer of dead keratinocytes that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by **Cystic fibrosis)**. In the lower airways there are collectins in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is **colonised** with ‘good’ bacteria that form your microbiome.
33
_Anatomical Barriers to Infection_ * Skin has a dense layer of dead ... that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are ... in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
* Skin has a dense layer of dead **keratinocytes** that act as a physical barrier. * In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are **collectins** in the surfactant that can activate complement. * In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection. * In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens. * The intestine is colonised with ‘good’ bacteria that form your microbiome.
34
_Tissue Damage_ * Tissue resident cells detect the infection and release ... innate immune effectors and cytokines to cause vasodilation and recruitments of further innate immune cells.
* Tissue resident cells detect the infection and release **soluble** innate immune effectors and cytokines to cause vasodilation and recruitments of further innate immune cells.
35
_Tissue Damage_ * Tissue resident cells detect the infection and release soluble innate immune effectors and ... to cause vasodilation and recruitments of further innate immune cells.
* Tissue resident cells detect the infection and release soluble innate immune effectors and **cytokines** to cause vasodilation and recruitments of further innate immune cells.
36
_Tissue Damage_ * Tissue resident cells detect the infection and release soluble innate immune ... and cytokines to cause ... and recruitments of further innate immune cells.
* Tissue resident cells detect the infection and release soluble innate immune **effectors** and cytokines to cause **vasodilation** and recruitments of further innate immune cells.
37
_Soluble innate immune molecules_ * ... such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial ... * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce inflammation
* **Enzymes** such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial **peptides** * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce inflammation
38
_Soluble innate immune molecules_ * Enzymes such as Lysozyme * Disrupt bacterial cell ...; found in blood and tears * ... peptides * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for ... and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce inflammation
* Enzymes such as Lysozyme * Disrupt bacterial cell **walls**; found in blood and tears * **Antimicrobial** peptides * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for **phagocytosis** and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce inflammation
39
_Soluble innate immune molecules_ * Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial peptides * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate ... * ... components * Lyse bacteria, opsonise bacteria and induce inflammation
* Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial peptides * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate **complement** * **Complement** components * Lyse bacteria, opsonise bacteria and induce inflammation
40
_Soluble innate immune molecules_ * Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial peptides * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to ... targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, ... bacteria and induce inflammation
* Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial peptides * Disrupt microbial membranes * Collectins, ficolins and pentraxins * Bind to **pathogens** targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, **opsonise** bacteria and induce inflammation
41
_Soluble innate immune molecules_ * Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial peptides * Disrupt microbial ... * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce **...**
* Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in blood and tears * Antimicrobial peptides * Disrupt microbial **membranes** * Collectins, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce **inflammation**
42
_Soluble innate immune molecules_ * Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in ... and ... * Antimicrobial peptides * Disrupt microbial membranes * ... , ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce inflammation
* Enzymes such as Lysozyme * Disrupt bacterial cell walls; found in **blood** and **tears** * Antimicrobial peptides * Disrupt microbial membranes * **Collectins**, ficolins and pentraxins * Bind to pathogens targeting them for phagocytosis and activate complement * Complement components * Lyse bacteria, opsonise bacteria and induce inflammation
43
These are all examples of ... ... immune molecules
These are all examples of **soluble innate** immune molecules
44
Define opsonise
make (a foreign cell) more susceptible to phagocytosis.
45
_Lysozyme disrupts peptidoglycan_ * Lysozyme is secreted by phagocytes and ... cells from the small intestine * Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria. * Cleaves the bond between the alternating sugars that make up peptidoglycan * Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
* Lysozyme is secreted by phagocytes and **paneth** cells from the small intestine * Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria. * Cleaves the bond between the alternating sugars that make up peptidoglycan * Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
46
_Lysozyme disrupts peptidoglycan_ * Lysozyme is secreted by phagocytes and paneth cells from the small intestine * Lysozyme is most effective against gram ... bacteria because LPS masks peptidoglycan in gram ... bacteria. * Cleaves the bond between the alternating sugars that make up peptidoglycan * Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
* Lysozyme is secreted by phagocytes and paneth cells from the small intestine * Lysozyme is most effective against gram **positive** bacteria because LPS masks peptidoglycan in gram **negative** bacteria. * Cleaves the bond between the alternating sugars that make up peptidoglycan * Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
47
_Lysozyme disrupts peptidoglycan_ * Lysozyme is secreted by phagocytes and paneth cells from the small intestine * Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria. * ... the bond between the alternating sugars that make up peptidoglycan * Phospholipase ... hydrolyses phospholipids in cell membrane to kill bacteria
* Lysozyme is secreted by phagocytes and paneth cells from the small intestine * Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria. * **Cleaves** the bond between the alternating sugars that make up peptidoglycan * Phospholipase **A2** hydrolyses phospholipids in cell membrane to kill bacteria
48
Lysozyme is most effective against gram ... bacteria because LPS masks peptidoglycan in gram ... bacteria.
Lysozyme is most effective against gram **positive** bacteria because LPS masks peptidoglycan in gram **negative** bacteria.
49
_Antimicrobial peptides - 3 Families_ * ... * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * Cathelicidins * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * Defensins * 2 classes - alpha, beta defensins
* **Histatins** * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * Cathelicidins * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * Defensins * 2 classes - alpha, beta defensins
50
_Antimicrobial peptides - 3 Families_ * Histatins * Produced in the ... cavity. Active against pathogenic fungi, e.g. Candida albicans * Cathelicidins * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * ... * 2 classes - alpha, beta ...
* Histatins * Produced in the **oral** cavity. Active against pathogenic fungi, e.g. Candida albicans * Cathelicidins * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * **Defensins** * 2 classes - alpha, beta **defensins**
51
_Antimicrobial peptides - 3 Families_ * Histatins * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * C... * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * Defensins * 2 classes - alpha, beta defensins
* Histatins * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * **Cathelicidins** * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * Defensins * 2 classes - alpha, beta defensins
52
_Antimicrobial peptides - 3 Families_ * Histatins * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * Cathelicidins * LL-... broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * Defensins * 2 classes - ..., ... defensins
* Histatins * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * Cathelicidins * LL-**37** broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * Defensins * 2 classes - **alpha, beta** defensins
53
_Antimicrobial peptides_ * 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in ... * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
* 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in **saliva** * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
54
_Antimicrobial peptides_ * 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by ..., epithelial cells and ... cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
* 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by **neutrophils**, epithelial cells and **paneth** cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
55
_Antimicrobial peptides_ * 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in ..., by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
* 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in **minutes**, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
56
_Antimicrobial peptides_ * 3 families - Histatins, Cathlicidins, Defensins * Cover ... surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
* 3 families - Histatins, Cathlicidins, Defensins * Cover **epithelial** surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit DNA and RNA synthesis
57
_Antimicrobial peptides_ * 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit ... and ... synthesis
* 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack fungi, viruses (influenza and herpes virus) * Inhibit **DNA** and **RNA** synthesis
58
_Antimicrobial peptides_ * 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack ..., ... (influenza and herpes virus) * Inhibit DNA and RNA synthesis
* 3 families - Histatins, Cathlicidins, Defensins * Cover epithelial surfaces, found in saliva * Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine * Kill bacteria in minutes, by disrupting the membrane * Also attack **fungi, viruses** (influenza and herpes virus) * Inhibit DNA and RNA synthesis
59
Antimicrobial peptides kill bacteria how quickly?
in minutes - slowest takes 90 mins
60
Antimicrobial peptides can also attack ... and ...
fungi and viruses (influenza and herpes virus)
61
Antimicrobial peptides inhibit ... and ... synthesis
Antimicrobial peptides inhibit **DNA** and **RNA** synthesis
62
... cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the healthy new born
**Defensins** cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the healthy new born
63
Defensins cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the ... ... ...
Defensins cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the **healthy new born**
64
The only human cathelicidin is ..., a peptide of ... amino acids synthesized by macrophages, neutrophils, and epithelial cells (providing antimicrobial protection to our skin and the lining of our urinary tract).
The only human cathelicidin is **LL37**, a peptide of **37** amino acids synthesized by macrophages, neutrophils, and epithelial cells (providing antimicrobial protection to our skin and the lining of our urinary tract).
65
_Defensins_ * ...-... aa amphipathic peptides which means they have both hydrophilic and hydrophobic regions on their cell surface. * Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region * Disrupt microbial membranes but not that of the host
* **35-40** aa amphipathic peptides which means they have both hydrophilic and hydrophobic regions on their cell surface. * Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region * Disrupt microbial membranes but not that of the host
66
_Defensins_ * 35-40 aa ... peptides which means they have both hydrophilic and hydrophobic regions on their cell surface. * Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region * Disrupt microbial membranes but not that of the ...
* 35-40 aa **amphipathic** peptides which means they have both hydrophilic and hydrophobic regions on their cell surface. * Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region * Disrupt microbial membranes but not that of the **host**
67
Defensins disrupt microbial membranes but not that of the ...
host
68
Defensins - ... bonds stabilise the structure to have a positively charged region separated from a hydrophobic region
Defensins - **Disulphide** bonds stabilise the structure to have a positively charged region separated from a hydrophobic region
69
Defensins are amphipathic, i.e. they have ... charge separated from a ... region.
Defensins are amphipathic, i.e. they have **positive** charge separated from a **hydrophobic** region.
70
_Collectins, ficolins and pentraxins_ * Collectins have globular lectin like heads that bind bacterial cell surface sugars. ... acid hides mannose antigens on host cells. * Ficolins (have a Fibrinogen like domain) recognise ... compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
* Collectins have globular lectin like heads that bind bacterial cell surface sugars. **Sialic** acid hides mannose antigens on host cells. * Ficolins (have a Fibrinogen like domain) recognise **acylated** compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
71
_Collectins, ficolins and pentraxins_ * Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides ... antigens on host cells. * Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. ...-... protein (...) is used as a clinical measure of inflammation – ... binds to phosphocholine on bacterial surfaces
* Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides **mannose** antigens on host cells. * Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. **C-reactive** protein (**CRP**) is used as a clinical measure of inflammation – **CRP** binds to phosphocholine on bacterial surfaces
72
_Collectins, ficolins and pentraxins_ * Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells. * Ficolins (have a ... like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
* Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells. * Ficolins (have a **Fibrinogen** like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
73
_Collectins, ficolins and pentraxins_ * Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells. * Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to ... on bacterial surfaces
* Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells. * Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls * Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to **phosphocholine** on bacterial surfaces
74
Collectins (collagen-containing C-type lectins) are a part of the innate immune system - Found in surfactant (surfactant protein A and D) and serum (MBL) Sialic acid can "hide" mannose antigens on the surface of host cells or bacteria from mannose-binding lectin. This prevents activation of ...
Collectins (collagen-containing C-type lectins) are a part of the innate immune system - Found in surfactant (surfactant protein A and D) and serum (MBL) Sialic acid can "hide" mannose antigens on the surface of host cells or bacteria from mannose-binding lectin. This prevents activation of **complement**.
75
... (collagen-containing C-type lectins) are a part of the innate immune system - Found in surfactant (surfactant protein A and D) and serum (MBL) Sialic acid can "hide" mannose antigens on the surface of host cells or bacteria from mannose-binding lectin. This prevents activation of complement.
**Collectins** (collagen-containing C-type lectins) are a part of the innate immune system - Found in surfactant (surfactant protein A and D) and serum (MBL) Sialic acid can "hide" mannose antigens on the surface of host cells or bacteria from mannose-binding lectin. This prevents activation of complement.
76
_Actions of Collectins, ficolins and pentraxins_ * Soluble ... ... receptors * Act as opsonins that bind to pathogens and infected cells targeting them for phagocytosis * Activate complement through the classical pathway/lectin pathway
* Soluble **pattern recognition receptors** * Act as opsonins that bind to pathogens and infected cells targeting them for phagocytosis * Activate complement through the classical pathway/lectin pathway
77
_Actions of Collectins, ficolins and pentraxins_ * Soluble pattern recognition receptors * Act as ... that bind to pathogens and infected cells targeting them for phagocytosis * Activate ... through the classical pathway/lectin pathway
* Soluble pattern recognition receptors * Act as **opsonins** that bind to pathogens and infected cells targeting them for phagocytosis * Activate **complement** through the classical pathway/lectin pathway
78
_Complement pathways converge on C3_ * 3 different pathways - ... pathway, ... pathway, ... pathway * Converge on C3 convertase leading to downstream events that induce inflammation
* 3 different pathways - **Classical** pathway, **Lectin** pathway, **Alternative** pathway * Converge on C3 convertase leading to downstream events that induce inflammation
79
_Complement pathways converge on C3_ * 3 different pathways - Classical pathway, ... pathway, Alternative pathway * Converge on C3 convertase leading to downstream events that induce ...
* 3 different pathways - Classical pathway, **Lectin** pathway, Alternative pathway * Converge on C3 convertase leading to downstream events that induce **inflammation**
80
_Complement System_ * Series of over ... proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
* Series of over **30** proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
81
_Complement System_ * Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a ... of reactions that ... the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
* Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a **cascade** of reactions that **amplify** the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
82
_Complement System_ * Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate ... and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
* Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate **inflammation** and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
83
_Complement System_ * Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the ... but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
* Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the **liver** but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
84
_Complement System_ * Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by ..., ... and epithelial cells of the intestine and urinary tract
* Series of over 30 proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by **monocytes**, **macrophages** and epithelial cells of the intestine and urinary tract
85
_Complement System_ * Series of over ... proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
* Series of over **30** proteins that constantly circulate in blood and fluids that bathe the body tissues * When they detect presence of foreign material, they initiate a cascade of reactions that amplify the signal * When activated, cooperate with other host defense systems to generate inflammation and rapidly remove the pathogen * Most made by the liver but also produced by monocytes, macrophages and epithelial cells of the **intestine** and **urinary** tract
86
_Complement components_ * Circulate as a ...-form (...) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have proteolytic enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
* Circulate as a **pro**-form (**inactive**) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have proteolytic enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
87
_Complement components_ * Circulate as a ...-form (...) in the blood * Numbered in the order they were ..., not in the order they are ... * Some have proteolytic enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
* Circulate as a **pro**-form (**inactive**) in the blood * Numbered in the order they were **discovered**, not in the order they are **activated** * Some have proteolytic enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
88
_Complement components_ * Circulate as a ...-form (...) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have ... enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
* Circulate as a **pro**-form (**inactive**) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have **proteolytic** enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
89
_Complement components_ * Circulate as a ...-form (...) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have proteolytic enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘...’ is the small fragment - except ...
* Circulate as a **pro**-form (**inactive**) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have proteolytic enzymatic activity * On activation they split into a small and large fragments triggering an amplification cascade * Normally ‘**a**’ is the small fragment - except **c2a**
90
_Complement components_ * Circulate as a pro-form (inactive) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have proteolytic enzymatic activity * On activation they split into a ... and ... fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
* Circulate as a pro-form (inactive) in the blood * Numbered in the order they were discovered, not in the order they are activated * Some have proteolytic enzymatic activity * On activation they split into a **small** and **large** fragments triggering an amplification cascade * Normally ‘a’ is the small fragment - except c2a
91
Complement components - Normally 'a' is the ... fragment - except c2a
Complement components - Normally 'a' is the **small** fragment - except c2a
92
_Complement Cascade_
93
_Effects mediated by complement components_
* Immune complexes bind CR1 receptors on the erythrocytes which transport them to phagocytes in the liver and spleen for removal. * Some components are termed anaphylatoxins because they can cause anaphylactic shock (C3a, C4a and C5a). * Changes induced by complement components leads to recruitment immune cells to the site of the infection and increases phagocytic capacity.
94
_Classical pathway (Complement)_ * Initiated by ... activation * C... is a complex of three proteins: C...q, C..r and C..s * The structure of C... is dominated by C...q * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C.. complex is stabilised by Ca2+ ions.
* Initiated by **C1** activation * **C1** is a complex of three proteins: C1q, C1r and C1s * The structure **of C1** is dominated by C1q * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * **C1** complex is stabilised by Ca2+ ions.
95
_Classical pathway (Complement)_ * Initiated by C1 activation * C1 is a complex of three proteins: C1q, C1... and C1... * The structure of C1 is dominated by C1q * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C1 complex is stabilised by Ca2+ ions.
* Initiated by C1 activation * C1 is a complex of three proteins: C1q**, C1r and C1s** * The structure of C1 is dominated by C1q * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C1 complex is stabilised by Ca2+ ions.
96
_Classical pathway (Complement)_ * Initiated by C1 activation * C1 is a complex of three proteins: C1q, C1r and C1s * The structure of C1 is dominated by C1... * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C1 complex is stabilised by Ca2+ ions.
* Initiated by C1 activation * C1 is a complex of three proteins: C1q, C1r and C1s * The structure of C1 is dominated by **C1q** * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C1 complex is stabilised by Ca2+ ions.
97
_Classical pathway (Complement)_ * Initiated by C1 activation * C1 is a complex of three proteins: C1q, C1r and C1s * The structure of C1 is dominated by C1q * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C1 complex is stabilised by ...+ ions.
* Initiated by C1 activation * C1 is a complex of three proteins: C1q, C1r and C1s * The structure of C1 is dominated by C1q * a large molecule of 18 polypeptides that form six collagen like triple helix structures * This was the first complement pathway to be discovered. * C1 complex is stabilised by **Ca2**+ ions.
98
_Classical pathway: Activation (Complement)_ * Triggered when C1 binds to the ... region of an antibody – antigen complex * C1 must bind at least 2 ... domains * IgM is the most efficient at activating complement as it has 5 ... domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
* Triggered when C1 binds to the **Fc** region of an antibody – antigen complex * C1 must bind at least 2 **FC** domains * IgM is the most efficient at activating complement as it has 5 **Fc** domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
99
_Classical pathway: Activation (Complement)_ * Triggered when C1 binds to the Fc region of an antibody – antigen complex * C1 must bind at least ... FC domains * IgM is the most efficient at activating complement as it has ... Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
* Triggered when C1 binds to the Fc region of an antibody – antigen complex * C1 must bind at least **2** FC domains * IgM is the most efficient at activating complement as it has **5** Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
100
_Classical pathway: Activation (Complement)_ * Triggered when C1 binds to the Fc region of an antibody – antigen complex * C1 must bind at least 2 FC domains * ... is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
* Triggered when C1 binds to the Fc region of an antibody – antigen complex * C1 must bind at least **2** FC domains * **IgM** is the most efficient at activating complement as it has **5** Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
101
... is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
**IgM** is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
102
IgM is the most efficient at activating complement as it has 5 Fc domains. ... and ..., and to a lesser extent ... can also activate complement when close together bound to antigen
IgM is the most efficient at activating complement as it has 5 Fc domains. **IgG1** and **IgG3**, and to a lesser extent **IgG2** can also activate complement when close together bound to antigen (The classical pathway is not activated by IgG4.)
103
The C1 protein is composed of three different types of subunits called C1..., C1r, and C1...
The C1 protein is composed of three different types of subunits called **C1q**, C1r, and **C1s**
104
One IgM molecule bound to antigen can activate complement, whereas around1000 IgG molecules may be required to get 2 close enough together to both bind to ...
One IgM molecule bound to antigen can activate complement, whereas around1000 IgG molecules may be required to get 2 close enough together to both bind to **C1 .**
105
C1 binding an immune complex allows for a conformational change that exposes the C1... binding site.
C1 binding an immune complex allows for a conformational change that exposes the **C1q** binding site.
106
_Serum IgM - Complement_ * Serum IgM cannot bind C1 as it has a ... conformation, the shape changes on binding antigen to reveal binding sites for C1q
* Serum IgM cannot bind C1 as it has a **planar** conformation, the shape changes on binding antigen to reveal binding sites for C1q
107
Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1...
Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for **C1q**
108
Serum ... cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
Serum **IgM** cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
109
_Classical pathway: Amplification_ * Binding C1q with the Fc domain causes a conformational change in C1... * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
* Binding C1q with the Fc domain causes a conformational change in **C1r** * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
110
_Classical pathway: Amplification_ * Binding C1q with the Fc domain causes a conformational change in C1r * C1... is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
* Binding C1q with the Fc domain causes a conformational change in C1r * **C1s** is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
111
_Classical pathway: Amplification_ * Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C... and C... splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
* Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate **C2 and C4** splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
112
_Classical pathway: Amplification_ * Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C.. convertase (C4b2a) can then activate over 200 C... molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
* Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * **C3** convertase (C4b2a) can then activate over 200 **C3** molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
113
_Classical pathway: Amplification_ * Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the ... convertase that activates ... leading to the membrane attack complex
* Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4b, C2a and C3b fragments form the **C5** convertase that activates **C5** leading to the membrane attack complex
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_Classical pathway: Amplification_ * Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * C4..., C2... and C3... fragments form the C5 convertase that activates C5 leading to the membrane attack complex
* Binding C1q with the Fc domain causes a conformational change in C1r * C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments * C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal * **C4b, C2a and C3b** fragments form the C5 convertase that activates C5 leading to the membrane attack complex
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C3a mediates ...
C3a mediates **inflammation**
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_Lectin pathway (Complement)_ * Antibody ..., activated by ficolins and ... binding lectin (MBL) * MBL binds ... residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases) * Active complex cleaves C2 and C4
* Antibody **independent**, activated by ficolins and mannose binding lectin (MBL) * MBL binds **mannose** residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases) * Active complex cleaves C2 and C4
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_Lectin pathway (Complement)_ * Antibody independent, activated by ... and mannose binding lectin (MBL) * MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases) * Active complex cleaves ... and ...
* Antibody independent, activated by **ficolins** and mannose binding lectin (MBL) * MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases) * Active complex cleaves **C2 and C4**
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_Lectin pathway (Complement)_ * Antibody independent, activated by ficolins and mannose binding lectin (MBL) * MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with ...-1 and ...-2 (serine proteases) * Active complex cleaves C2 and C4
* Antibody independent, activated by ficolins and mannose binding lectin (MBL) * MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with **MASP-1 and MASP-2** (serine proteases) * Active complex cleaves C2 and C4
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_Lectin pathway (Complement)_ * Antibody independent, activated by ficolins and ... * ... binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding ... forms a complex with MASP-1 and MASP-2 (... proteases) * Active complex cleaves C2 and C4
* Antibody independent, activated by ficolins and **mannose binding lectin (MBL)** * **MBL** binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses * Similar downstream mechanism to the classical pathway * Upon binding MBL forms a complex with MASP-1 and MASP-2 (**serine** proteases) * Active complex cleaves C2 and C4
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... is a member of the collectin family that is structurally similar to C1q
**MBL** is a member of the collectin family that is structurally similar to C1q
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MBL is a member of the ... family that is structurally similar to C1q
MBL is a member of the **collectin** family that is structurally similar to C1q
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MBL is a member of the collectin family that is structurally similar to ...
MBL is a member of the collectin family that is structurally similar to **C1q**
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MASP1 and 2 structurally and behaviourally similar to c1... and c1...
MASP1 and 2 structurally and behaviourally similar to **c1r and c1s.**
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People deficient in ... or MASP2 have recurrent respiratory infections in childhood before the adaptive defences develop.
People deficient in **MBL** or MASP2 have recurrent respiratory infections in childhood before the adaptive defences develop.
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People deficient in MBL or ... have recurrent respiratory infections in childhood before the adaptive defences develop.
People deficient in MBL or **MASP2** have recurrent respiratory infections in childhood before the adaptive defences develop.
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_Alternative pathway (Complement)_ * C3 spontaneous ... into C3... and C3... * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
* C3 spontaneous **hydrolyses** into **C3a and C3b** * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
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_Alternative pathway (Complement)_ * C3 spontaneous hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor ..., making it susceptible to cleavage by factor ... to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
* C3 spontaneous hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor **B**, making it susceptible to cleavage by factor **D** to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
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_Alternative pathway (Complement)_ * C3 spontaneous hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of ... min, unless it binds the serum protein properdin, which extends it half-life to ... min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
* C3 spontaneous hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of **5** min, unless it binds the serum protein properdin, which extends it half-life to **30** min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
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_Alternative pathway (Complement)_ * C3 ... hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can ... the signal
* C3 **spontaneous** hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can **amplify** the signal
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The ... pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
The **Alternative** pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
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The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor ... (circulates in the blood), factor ... (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor **B** (circulates in the blood), factor **D** (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
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The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and ... (released by monocytes and neutrophils).
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and **properdin** (released by monocytes and neutrophils).
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The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the ...), factor D (secreted by adipocytes), and properdin (released by ... and ...).
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the **blood**), factor D (secreted by adipocytes), and properdin (released by **monocytes** and **neutrophils**).
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_Alternative pathway (Complement)_ * C3 ... hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein ..., which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can ... the signal
* C3 **spontaneous** hydrolyses into C3a and C3b * C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb * C3bBb has a half-life of 5 min, unless it binds the serum protein **properdin**, which extends it half-life to 30 min by protecting it from proteases * C3b,Bb can hydrolyse more C3 creating more C3b which can **amplify** the signal
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Complement pathways - Overview
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_Terminal complement components_
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_Membrane attack complex_ * MAC forms a ... that inserts into the membrane allowing diffusion of ions and small molecules, ... moves into the cell killing it * Human cells have soluble and cell surface associated proteins that prevent MAC formation
* MAC forms a **pore** that inserts into the membrane allowing diffusion of ions and small molecules, **water** moves into the cell killing it * Human cells have soluble and cell surface associated proteins that prevent MAC formation
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_Membrane attack complex_ * MAC forms a pore that inserts into the membrane allowing diffusion of ions and small molecules, water moves into the cell killing it * ... cells have soluble and cell surface associated proteins that prevent MAC formation
* MAC forms a pore that inserts into the membrane allowing diffusion of ions and small molecules, water moves into the cell killing it * **Human** cells have soluble and cell surface associated proteins that prevent MAC formation
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_Complement pathway summary_
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_Complement inhibitors_ * Unwanted ... if no inhibitors * Hereditary Angioedema : C1 inhibitor deficiency * Classical complement cascade easily activated but can be treated with an injection of C1 inhibitor
* Unwanted **inflammation** if no inhibitors * Hereditary Angioedema : C1 inhibitor deficiency * Classical complement cascade easily activated but can be treated with an injection of C1 inhibitor
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_Complement inhibitors_ * Unwanted inflammation if no inhibitors * Hereditary Angioedema : C... inhibitor deficiency * Classical complement cascade easily activated but can be treated with an injection of C... inhibitor
* Unwanted inflammation if no inhibitors * Hereditary Angioedema : **C1** inhibitor deficiency * Classical complement cascade easily activated but can be treated with an injection of **C1** inhibitor
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Hereditary ... : C1 inhibitor deficiency
Hereditary **Angioedema** : C1 inhibitor deficiency
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Hereditary Angioedema : ... inhibitor deficiency
Hereditary Angioedema : **C1** inhibitor deficiency
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_Complement deficiency_ * Patients deficient of components of the complement pathway experience ... ... * MBL deficiency causes serious pyogenic infections in neonates and children * C3 deficiency is the most severe leading to successive severe infections * Patients deficient of C8 are prone to infection with Neisseria meningitis
* Patients deficient of components of the complement pathway experience **recurrent** **infections** * MBL deficiency causes serious pyogenic infections in neonates and children * C3 deficiency is the most severe leading to successive severe infections * Patients deficient of C8 are prone to infection with Neisseria meningitis
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_Complement deficiency_ * Patients deficient of components of the complement pathway experience recurrent infections * ... deficiency causes serious pyogenic infections in neonates and children * C3 deficiency is the most severe leading to successive severe infections * Patients deficient of C8 are prone to infection with Neisseria meningitis
* Patients deficient of components of the complement pathway experience recurrent infections * **MBL** deficiency causes serious pyogenic infections in neonates and children * C3 deficiency is the most severe leading to successive severe infections * Patients deficient of C8 are prone to infection with Neisseria meningitis
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_Complement deficiency_ * Patients deficient of components of the complement pathway experience recurrent infections * MBL deficiency causes serious pyogenic infections in neonates and children * ... deficiency is the most severe leading to successive severe infections * Patients deficient of C8 are prone to infection with Neisseria meningitis
* Patients deficient of components of the complement pathway experience recurrent infections * MBL deficiency causes serious pyogenic infections in neonates and children * **C3** deficiency is the most severe leading to successive severe infections * Patients deficient of C8 are prone to infection with Neisseria meningitis
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_Complement deficiency_ * Patients deficient of components of the complement pathway experience recurrent infections * MBL deficiency causes serious pyogenic infections in neonates and children * C3 deficiency is the most severe leading to successive severe infections * Patients deficient of ... are prone to infection with Neisseria meningitis
* Patients deficient of components of the complement pathway experience recurrent infections * MBL deficiency causes serious pyogenic infections in neonates and children * C3 deficiency is the most severe leading to successive severe infections * Patients deficient of **C8** are prone to infection with Neisseria meningitis
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Patients deficient of C8 are prone to infection with Neisseria ....
Patients deficient of C8 are prone to infection with Neisseria **meningitis**
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Patients deficient of ... are prone to infection with Neisseria meningitis
Patients deficient of **C8** are prone to infection with Neisseria meningitis
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C... deficiency is the most severe leading to successive severe infections
**C3** deficiency is the most severe leading to successive severe infections
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MBL deficiency causes serious ... infections in neonates and children
MBL deficiency causes serious **pyogenic** infections in neonates and children
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... deficiency causes serious pyogenic infections in neonates and children
**MBL** deficiency causes serious pyogenic infections in neonates and children
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MBL deficiency causes serious pyogenic infections in what groups of people?
MBL deficiency causes serious pyogenic infections in **neonates and children**
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_Complement deficiency in SLE_ * ...% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE) * C4 deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen. * Phagocytes recognise the immune complexes via their Fc receptors and engulf them
* **90**% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE) * C4 deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen. * Phagocytes recognise the immune complexes via their Fc receptors and engulf them
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_Complement deficiency in SLE_ * 90% of people deficient for C4 develop the autoimmune disease systemic ... ... (SLE) * C4 deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen. * Phagocytes recognise the immune complexes via their Fc receptors and engulf them
* 90% of people deficient for C4 develop the autoimmune disease systemic **lupus erythematosus** (SLE) * C4 deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen. * Phagocytes recognise the immune complexes via their Fc receptors and engulf them
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_Complement deficiency in SLE_ * 90% of people deficient for C... develop the autoimmune disease systemic lupus erythematosus (SLE) * C... deficiency means less C3b (C...b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen. * Phagocytes recognise the immune complexes via their Fc receptors and engulf them
* 90% of people deficient for **C4** develop the autoimmune disease systemic lupus erythematosus (SLE) * **C4** deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen. * Phagocytes recognise the immune complexes via their Fc receptors and engulf them
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_Complement deficiency in SLE_ * 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE) * C4 deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the ... and ... * Phagocytes recognise the immune complexes via their ... receptors and engulf them
* 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE) * C4 deficiency means less C3b (C4b2a is C3 convertase) * C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the **liver** and **spleen**. * Phagocytes recognise the immune complexes via their **Fc** receptors and engulf them
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What % of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)?
**90**% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
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List another family of antimicrobial peptides in humans, other than defensins
* **Histatins** * Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans * **Cathelicidins** * LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria * (Defensins) * Two classes – α, β defensins
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Antimicrobial peptides inhibit...
DNA and RNA synthesis